Preliminary studies have shown that sarcolemmal Na,K-ATPase (sodium pump) and sarcoplasmic reticulum Ca-ATPase (calcium pump) are inhibited by low concentrations of palmitylcarnitine. It has been reported that the level of palmitylcarnitine increases approximately three-fold in myocardial ischemia. The purpose of this proposal is to test the hypothesis that palmitylcarnitine may inhibit these pump systems in the ischemic myocardium and that this may contribute to the loss of contractility. In order to do this it will first be necessary to determine the conditions in which Na,K-ATPase and Ca-ATPase are inhibited by palmitylcarnitine (pH, ion concentrations), whether inhibition is reversible, and to what extent structurally related compounds such as fatty acids, palmityl-CoA, myristylcarnitine and phospholipids can themselves inhibit these enzymes or protect them against inhibition by palmitylcarnitine. The effects of palmitylcarnitine will then be tested on calcium uptake and release by cardiac sarcoplasmic reticulum and on ATP-dependent Na-K-transport in liposomes containing cardiac Na,K-ATPase or on Rb86 uptake by red cells or cultured heart cells. The subcellular distribution of C14-palmitylcarnitine in the myocardial cell will then be measured to see if the levels in the sarcolemmal and sarcoplasmic reticulum fractions are high enough that inhibition of their respective sodium and calcium pumps in vivo might be expected.